By the time a patient is seen by Robert B. Darnell, MD, Ph.D., that person is often in the late and irreversible stages of a devastating brain disease. Dr. Darnell, head of the Laboratory of Molecular Neuro-oncology at Rockefeller University in New York City, an Investigator at Howard Hughes Medical Institute, and an attending neurologist at Memorial Sloan Kettering Cancer Center, studies rare brain diseases called paraneoplastic neurologic disorders, or PNDs. PNDs are thought to be triggered by the body's immune response to certain cancers, including breast and ovarian cancer.
Dr. Darnell relates the story of one typical PND patient, a middle-aged woman who woke up one morning with sudden dizziness. Prior to this, she had been perfectly healthy. But her dizziness that morning was so severe that she felt sick to her stomach. She fell from feeling imbalanced and her hands shook. While her cognitive function, vision, and strength were all normal, her coordination was completely and irreversibly lost.
When Darnell ordered tests, he found that the patient had tons of white blood cells in her spinal fluid. "We now know that what happened is that she had breast cancer, although it had not gotten into her brain," says Darnell. "The speculation is that it had been there for a long period of time. What starts PND is cancer, which triggers the immune response." In other words, the immune system effectively fights the cancer in the body of these PND patients, but it somehow also crosses the blood-brain barrier and begins attacking brain tissue as well, with devastating effects.
As tragic as these cases are, says Darnell, they may provide crucial information that could one day lead to a cancer vaccine. "These diseases, in my view, are the Rosetta Stones," says Darnell. From these patients, researchers can derive answers to questions such as how the immune system targets a protein found in these cancer cells to destroy the cancer, what goes wrong when this immune system response begins to attack nerve cells in the brain, and why this happens in some people but not in others.
Listening to Darnell talk, one is struck by his quiet resolve and the undeniable integrity that imbues his research, his work with patients, and his life. Darnell himself traces the roots of his interest in science and medicine -- as well as his desire to help people -- to his upbringing.
As a child, Darnell sat at the dinner table, listening to his father, James Darnell, MD, a renowned pioneer in molecular biology and gene regulation, talk about his work. "My mother would ask him to talk about what he's working on and I would see him convey excitement about what he's doing," recalls Darnell. "Dad was at the birthplace of the molecular biology revolution."
The senior Dr. Darnell was also a humanitarian and a champion for peace. "The Vietnam War was going on and he was one of the leaders of the professors against war," says Darnell. "It stimulated my own sense of liberalism and it inspired me to apply what I do to real life. For me, this progressed to science."
His parents, says Darnell, encouraged him to pursue a joint MD and Ph.D. program -- a suggestion he initially didn't want to follow because he thought going to medical school would be the best way for him to help people. "I had this idealistic urge to do something for humanity," says Darnell. "I was a young man and rebellious. I was not interested in being in an ivory tower, and wanted to do something relevant to humanitarian causes."
Darnell did eventually decide to enroll in a joint MD-Ph.D. program at Washington University, and upon graduation, eventually became interested in neuroscience and tumor biology. "I became enamored with the idea of doing something to help people and find something beautiful and new," says Darnell.
Today, Dr. Darnell's laboratory is working on both the development of cancer vaccines and conducting research on PND antigens. By studying the tumor-killing T-cells in PND patients, doctors have found a way to transform normal T-cells into ones that can recognize and attack breast and ovarian tumors. Half of the lab is working on customized therapy and the other is working on translational research, says Darnell.
Similarly, Dr. Darnell also splits his time, working in the lab as well as seeing patients and teaching as an attending neurologist. True to his goal, he is doing what he set out to do as a young man -- help people -- both as a researcher and as a physician. And perhaps most commendably, he is doing it with care and with respect for his patients. Referring to his work, he says, "It's something patients are teaching us. They are coming here and helping us."